Clinical and Vaccine Immunology最新文献

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Correction for Nishimori et al., “Identification of an Atypical Enzootic Bovine Leukosis in Japan by Using a Novel Classification of Bovine Leukemia Based on Immunophenotypic Analysis” 修正Nishimori等人的“利用基于免疫表型分析的牛白血病新分类鉴定日本非典型地方性牛白血病”
Clinical and Vaccine Immunology Pub Date : 2018-04-17 Print Date: 2017-12-01 DOI: 10.1128/CVI.00001-18
Asami Nishimori, Satoru Konnai, Tomohiro Okagawa, Naoya Maekawa, Shinya Goto, Ryoyo Ikebuchi, Ayako Nakahara, Yuzumi Chiba, Masaho Ikeda, Shiro Murata, Kazuhiko Ohashi
{"title":"Correction for Nishimori et al., “Identification of an Atypical Enzootic Bovine Leukosis in Japan by Using a Novel Classification of Bovine Leukemia Based on Immunophenotypic Analysis”","authors":"Asami Nishimori, Satoru Konnai, Tomohiro Okagawa, Naoya Maekawa, Shinya Goto, Ryoyo Ikebuchi, Ayako Nakahara, Yuzumi Chiba, Masaho Ikeda, Shiro Murata, Kazuhiko Ohashi","doi":"10.1128/CVI.00001-18","DOIUrl":"https://doi.org/10.1128/CVI.00001-18","url":null,"abstract":"Published 17 April 2018 Citation Nishimori A, Konnai S, Okagawa T, Maekawa N, Goto S, Ikebuchi R, Nakahara A, Chiba Y, Ikeda M, Murata S, Ohashi K. 2018. Correction for Nishimori et al., “Identification of an atypical enzootic bovine leukosis in Japan by using a novel classification of bovine leukemia based on immunophenotypic analysis.” Clin Vaccine Immunol 24:e00001-18. https://doi.org/10.1128/CVI.00001-18. Copyright © 2018 American Society for Microbiology. All Rights Reserved. This author correction was added to the December 2017 issue of Clinical and Vaccine Immunology. As of January 2018, research on vaccines and clinical and diagnostic immunology is published by ASM's multidisciplinary, open-access journal mSphere®. AUTHOR CORRECTION","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00001-18","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36083038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
GI-19007, a Novel Saccharomyces cerevisiae-Based Therapeutic Vaccine against Tuberculosis. GI-19007,一种基于酿酒酵母的新型结核病治疗性疫苗。
Clinical and Vaccine Immunology Pub Date : 2017-12-05 Print Date: 2017-12-01 DOI: 10.1128/CVI.00245-17
Thomas H King, Crystal A Shanley, Zhimin Guo, Donald Bellgrau, Timothy Rodell, Synthia Furney, Marcela Henao-Tamayo, Ian M Orme
{"title":"GI-19007, a Novel Saccharomyces cerevisiae-Based Therapeutic Vaccine against Tuberculosis.","authors":"Thomas H King,&nbsp;Crystal A Shanley,&nbsp;Zhimin Guo,&nbsp;Donald Bellgrau,&nbsp;Timothy Rodell,&nbsp;Synthia Furney,&nbsp;Marcela Henao-Tamayo,&nbsp;Ian M Orme","doi":"10.1128/CVI.00245-17","DOIUrl":"https://doi.org/10.1128/CVI.00245-17","url":null,"abstract":"<p><p>As yet, very few vaccine candidates with activity in animals against <i>Mycobacterium tuberculosis</i> infection have been tested as therapeutic postexposure vaccines. We recently described two pools of mycobacterial proteins with this activity, and here we describe further studies in which four of these proteins (Rv1738, Rv2032, Rv3130, and Rv3841) were generated as a fusion polypeptide and then delivered in a novel yeast-based platform (Tarmogen) which itself has immunostimulatory properties, including activation of Toll-like receptors. This platform can deliver antigens into both the class I and class II antigen presentation pathways and stimulate strong Th1 and Th17 responses. In mice this fusion vaccine, designated GI-19007, was immunogenic and elicited strong gamma interferon (IFN-γ) and interleukin-17 (IL-17) responses; despite this, they displayed minimal prophylactic activity in mice that were subsequently infected with a virulent clinical strain. In contrast, in a therapeutic model in the guinea pig, GI-19007 significantly reduced the lung bacterial load and reduced lung pathology, particularly in terms of secondary lesion development, while significantly improving survival in one-third of these animals. In further studies in which guinea pigs were vaccinated with BCG before challenge, therapeutic vaccination with GI-19007 initially improved survival versus that of animals given BCG alone, although this protective effect was gradually lost at around 400 days after challenge. Given its apparent ability to substantially limit bacterial dissemination within and from the lungs, GI-19007 potentially can be used to limit lung damage as well as facilitating chemotherapeutic regimens in infected individuals.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00245-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35463536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
Progress toward Development of a Vaccine against Congenital Cytomegalovirus Infection. 先天性巨细胞病毒感染疫苗的研究进展
Clinical and Vaccine Immunology Pub Date : 2017-12-05 Print Date: 2017-12-01 DOI: 10.1128/CVI.00268-17
Mark R Schleiss, Sallie R Permar, Stanley A Plotkin
{"title":"Progress toward Development of a Vaccine against Congenital Cytomegalovirus Infection.","authors":"Mark R Schleiss, Sallie R Permar, Stanley A Plotkin","doi":"10.1128/CVI.00268-17","DOIUrl":"10.1128/CVI.00268-17","url":null,"abstract":"<p><p>A vaccine against congenital human cytomegalovirus (CMV) infection is a major public health priority. Congenital CMV causes substantial long-term morbidity, particularly sensorineural hearing loss (SNHL), in newborns, and the public health impact of this infection on maternal and child health is underrecognized. Although progress toward development of a vaccine has been limited by an incomplete understanding of the correlates of protective immunity for the fetus, knowledge about some of the key components of the maternal immune response necessary for preventing transplacental transmission is accumulating. Moreover, although there have been concerns raised about observations indicating that maternal seropositivity does not fully prevent recurrent maternal CMV infections during pregnancy, it is becoming increasing clear that preconception immunity does confer some measure of protection against both CMV transmission and CMV disease (if transmission occurs) in the newborn infant. Although the immunity to CMV conferred by both infection and vaccination is imperfect, there are encouraging data emerging from clinical trials demonstrating the immunogenicity and potential efficacy of candidate CMV vaccines. In the face of the knowledge that between 20,000 and 30,000 infants are born with congenital CMV in the United States every year, there is an urgent and compelling need to accelerate the pace of vaccine trials. In this minireview, we summarize the status of CMV vaccines in clinical trials and provide a perspective on what would be required for a CMV immunization program to become incorporated into clinical practice.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00268-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35463538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 81
A Single Intramuscular Dose of a Plant-Made Virus-Like Particle Vaccine Elicits a Balanced Humoral and Cellular Response and Protects Young and Aged Mice from Influenza H1N1 Virus Challenge despite a Modest/Absent Humoral Response. 单次肌内注射植物制造的病毒样颗粒疫苗可引起平衡的体液和细胞反应,并保护年轻和老年小鼠免受甲型H1N1流感病毒的攻击,尽管存在适度或不存在体液反应。
Clinical and Vaccine Immunology Pub Date : 2017-12-05 Print Date: 2017-12-01 DOI: 10.1128/CVI.00273-17
Breanna Hodgins, Karen K Yam, Kaitlin Winter, Stephane Pillet, Nathalie Landry, Brian J Ward
{"title":"A Single Intramuscular Dose of a Plant-Made Virus-Like Particle Vaccine Elicits a Balanced Humoral and Cellular Response and Protects Young and Aged Mice from Influenza H1N1 Virus Challenge despite a Modest/Absent Humoral Response.","authors":"Breanna Hodgins,&nbsp;Karen K Yam,&nbsp;Kaitlin Winter,&nbsp;Stephane Pillet,&nbsp;Nathalie Landry,&nbsp;Brian J Ward","doi":"10.1128/CVI.00273-17","DOIUrl":"https://doi.org/10.1128/CVI.00273-17","url":null,"abstract":"<p><p>Virus-like-particle (VLP) influenza vaccines can be given intramuscularly (i.m.) or intranasally (i.n.) and may have advantages over split-virion formulations in the elderly. We tested a plant-made VLP vaccine candidate bearing the viral hemagglutinin (HA) delivered either i.m. or i.n. in young and aged mice. Young adult (5- to 8-week-old) and aged (16- to 20-month-old) female BALB/c mice received a single 3-μg dose based on the HA (A/California/07/2009 H1N1) content of a plant-made H1-VLP (i.m. or i.n.) split-virion vaccine (i.m.) or were left naive. After vaccination, humoral and splenocyte responses were assessed, and some mice were challenged. Both VLP and split vaccines given i.m. protected 100% of the young animals, but the VLP group lost the least weight and had stronger humoral and cellular responses. Compared to split-vaccine recipients, aged animals vaccinated i.m. with VLP were more likely to survive challenge (80% versus 60%). The lung viral load postchallenge was lowest in the VLP i.m. groups. Mice vaccinated with VLP i.n. had little detectable immune response, but survival was significantly increased. In both age groups, i.m. administration of the H1-VLP vaccine elicited more balanced humoral and cellular responses and provided better protection from homologous challenge than the split-virion vaccine.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00273-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35597822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 22
Development of an Extended-Specificity Multiplex Immunoassay for Detection of Streptococcus pneumoniae Serotype-Specific Antigen in Urine by Use of Human Monoclonal Antibodies. 利用人单克隆抗体检测尿中肺炎链球菌血清型特异性抗原的扩展特异性多重免疫分析法的建立。
Clinical and Vaccine Immunology Pub Date : 2017-12-05 Print Date: 2017-12-01 DOI: 10.1128/CVI.00262-17
Seyi D Eletu, Carmen L Sheppard, Elizabeth Thomas, Kenneth Smith, Priya Daniel, David J Litt, Wei Shen Lim, Norman K Fry
{"title":"Development of an Extended-Specificity Multiplex Immunoassay for Detection of Streptococcus pneumoniae Serotype-Specific Antigen in Urine by Use of Human Monoclonal Antibodies.","authors":"Seyi D Eletu,&nbsp;Carmen L Sheppard,&nbsp;Elizabeth Thomas,&nbsp;Kenneth Smith,&nbsp;Priya Daniel,&nbsp;David J Litt,&nbsp;Wei Shen Lim,&nbsp;Norman K Fry","doi":"10.1128/CVI.00262-17","DOIUrl":"https://doi.org/10.1128/CVI.00262-17","url":null,"abstract":"<p><p>Current pneumococcal vaccines cover the 10 to 23 most common serotypes of the 92 presently described. However, with the increased usage of pneumococcal-serotype-based vaccines, the risk of serotype replacement and an increase in disease caused by nonvaccine serotypes remains. Serotype surveillance of pneumococcal infections relies heavily on culture techniques, which are known to be insensitive, particularly in cases of noninvasive disease. Pneumococcal-serotype-specific urine assays offer an alternative method of serotyping for both invasive and noninvasive disease. However, the assays described previously cover mainly conjugate vaccine serotypes, give little information about circulating nonvaccine serotypes, and are currently available only in one or two specialist laboratories. Our laboratory has developed a Luminex-based extended-range antigen capture assay to detect pneumococcal-serotype-specific antigens in urine samples. The assay targets 24 distinct serotypes/serogroups plus the cell wall polysaccharide (CWP) and some cross-reactive serotypes. We report that the assay is capable of detecting all the targeted serotypes and the CWP at 0.1 ng/ml, while some serotypes are detected at concentrations as low as 0.3 pg/ml. The analytical serotype specificity was determined to be 98.4% using a panel of polysaccharide-negative urine specimens spiked with nonpneumococcal bacterial antigens. We also report clinical sensitivities of 96.2% and specificities of 89.9% established using a panel of urine specimens from patients diagnosed with community-acquired pneumonia or pneumococcal disease. This assay can be extended for testing other clinical samples and has the potential to greatly improve serotype-specific surveillance in the many cases of pneumococcal disease in which a culture is never obtained.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00262-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35572980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 14
Identification of Novel Antigens Recognized by Serum Antibodies in Bovine Tuberculosis. 牛结核病血清抗体识别新抗原的鉴定。
Clinical and Vaccine Immunology Pub Date : 2017-12-05 Print Date: 2017-12-01 DOI: 10.1128/CVI.00259-17
Konstantin P Lyashchenko, Adrian Grandison, Karen Keskinen, Alina Sikar-Gang, Paul Lambotte, Javan Esfandiari, Gregory C Ireton, Aarthy Vallur, Steven G Reed, Gareth Jones, H Martin Vordermeier, Judy R Stabel, Tyler C Thacker, Mitchell V Palmer, W Ray Waters
{"title":"Identification of Novel Antigens Recognized by Serum Antibodies in Bovine Tuberculosis.","authors":"Konstantin P Lyashchenko,&nbsp;Adrian Grandison,&nbsp;Karen Keskinen,&nbsp;Alina Sikar-Gang,&nbsp;Paul Lambotte,&nbsp;Javan Esfandiari,&nbsp;Gregory C Ireton,&nbsp;Aarthy Vallur,&nbsp;Steven G Reed,&nbsp;Gareth Jones,&nbsp;H Martin Vordermeier,&nbsp;Judy R Stabel,&nbsp;Tyler C Thacker,&nbsp;Mitchell V Palmer,&nbsp;W Ray Waters","doi":"10.1128/CVI.00259-17","DOIUrl":"https://doi.org/10.1128/CVI.00259-17","url":null,"abstract":"<p><p>Bovine tuberculosis (TB), caused by <i>Mycobacterium bovis</i>, remains an important zoonotic disease posing a serious threat to livestock and wildlife. The current TB tests relying on cell-mediated and humoral immune responses in cattle have performance limitations. To identify new serodiagnostic markers of bovine TB, we screened a panel of 101 recombinant proteins, including 10 polyepitope fusions, by a multiantigen print immunoassay (MAPIA) with well-characterized serum samples serially collected from cattle with experimental or naturally acquired <i>M. bovis</i> infection. A novel set of 12 seroreactive antigens was established. Evaluation of selected proteins in the dual-path platform (DPP) assay showed that the highest diagnostic accuracy (∼95%) was achieved with a cocktail of five best-performing antigens, thus demonstrating the potential for development of an improved and more practical serodiagnostic test for bovine TB.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00259-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35472139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 19
The Legacy of CVI. CVI的遗产。
Clinical and Vaccine Immunology Pub Date : 2017-12-05 Print Date: 2017-12-01 DOI: 10.1128/CVI.00276-17
Marcela F Pasetti, Steven D Douglas, Susan F Plaeger
{"title":"The Legacy of CVI.","authors":"Marcela F Pasetti,&nbsp;Steven D Douglas,&nbsp;Susan F Plaeger","doi":"10.1128/CVI.00276-17","DOIUrl":"https://doi.org/10.1128/CVI.00276-17","url":null,"abstract":"<p><p><i>Clinical and Vaccine Immunology</i> (CVI) will merge with the American Society for Microbiology (ASM) open-access journal <i>mSphere</i> in January 2018. We commemorate this transition by exploring the history of CVI and that of its predecessor, <i>Clinical and Diagnostic Laboratory Immunology</i> (CDLI), and by acknowledging their contributors. Research on vaccines, clinical immunology, and clinical diagnostic immunology published through <i>mSphere</i> will be available without restrictions to an ever-larger audience, which will expedite progress in the field. ASM remains committed to supporting its members and the research community by facilitating the dissemination of scientific knowledge in these important areas.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00276-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35641336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stable Chromosomal Expression of Shigella flexneri 2a and 3a O-Antigens in the Live Salmonella Oral Vaccine Vector Ty21a. 福氏志贺氏菌2a和3a o型抗原在沙门氏菌口服活疫苗Ty21a中的稳定染色体表达
Clinical and Vaccine Immunology Pub Date : 2017-12-05 Print Date: 2017-12-01 DOI: 10.1128/CVI.00181-17
Madushini N Dharmasena, Manuel Osorio, Kazuyo Takeda, Scott Stibitz, Dennis J Kopecko
{"title":"Stable Chromosomal Expression of Shigella flexneri 2a and 3a O-Antigens in the Live Salmonella Oral Vaccine Vector Ty21a.","authors":"Madushini N Dharmasena,&nbsp;Manuel Osorio,&nbsp;Kazuyo Takeda,&nbsp;Scott Stibitz,&nbsp;Dennis J Kopecko","doi":"10.1128/CVI.00181-17","DOIUrl":"https://doi.org/10.1128/CVI.00181-17","url":null,"abstract":"<p><p>We have been exploring the use of the live attenuated <i>Salmonella enterica</i> serovar Typhi Ty21a vaccine strain as a versatile oral vaccine vector for the expression and delivery of multiple foreign antigens, including <i>Shigella</i> O-antigens. In this study, we separately cloned genes necessary for the biosynthesis of the <i>Shigella flexneri</i> serotype 2a and 3a O-antigens, which have been shown to provide broad cross-protection to multiple disease-predominant <i>S. flexneri</i> serotypes. The cloned <i>S. flexneri</i> 2a <i>rfb</i> operon, along with <i>bgt</i> and <i>gtrII</i>, contained on the SfII bacteriophage, was sufficient in Ty21a to express the heterologous <i>S. flexneri</i> 2a O-antigen containing the 3,4 antigenic determinants. Further, this <i>rfb</i> operon, along with <i>gtrA</i>, <i>gtrB</i>, and <i>gtrX</i> contained on the Sfx bacteriophage and <i>oac</i> contained on the Sf6 bacteriophage, was sufficient to express <i>S. flexneri</i> 3a O-antigen containing the 6, 7, and 8 antigenic determinants. Ty21a, with these plasmid-carried or chromosomally inserted genes, demonstrated simultaneous and stable expression of homologous <i>S</i> Typhi O-antigen plus the heterologous <i>S. flexneri</i> O-antigen. Candidate Ty21a vaccine strains expressing heterologous <i>S. flexneri</i> 2a or 3a lipopolysaccharide (LPS) elicited significant serum antibody responses against both homologous <i>S</i> Typhi and heterologous <i>Shigella</i> LPS and protected mice against virulent <i>S. flexneri</i> 2a or 3a challenges. These new <i>S. flexneri</i> 2a and 3a O-antigen-expressing Ty21a vaccine strains, together with our previously constructed Ty21a strains expressing <i>Shigella sonnei</i> or <i>Shigella dysenteriae</i> 1 O-antigens, have the potential to be used together for simultaneous protection against the predominant causes of shigellosis worldwide as well as against typhoid fever.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00181-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35463539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 16
High-Definition Mapping of Four Spatially Distinct Neutralizing Epitope Clusters on RiVax, a Candidate Ricin Toxin Subunit Vaccine. 候选蓖麻毒素亚单位疫苗RiVax上四个空间不同的中和表位簇的高清制图
Clinical and Vaccine Immunology Pub Date : 2017-12-05 Print Date: 2017-12-01 DOI: 10.1128/CVI.00237-17
Ronald T Toth, Siva Krishna Angalakurthi, Greta Van Slyke, David J Vance, John M Hickey, Sangeeta B Joshi, C Russell Middaugh, David B Volkin, David D Weis, Nicholas J Mantis
{"title":"High-Definition Mapping of Four Spatially Distinct Neutralizing Epitope Clusters on RiVax, a Candidate Ricin Toxin Subunit Vaccine.","authors":"Ronald T Toth,&nbsp;Siva Krishna Angalakurthi,&nbsp;Greta Van Slyke,&nbsp;David J Vance,&nbsp;John M Hickey,&nbsp;Sangeeta B Joshi,&nbsp;C Russell Middaugh,&nbsp;David B Volkin,&nbsp;David D Weis,&nbsp;Nicholas J Mantis","doi":"10.1128/CVI.00237-17","DOIUrl":"https://doi.org/10.1128/CVI.00237-17","url":null,"abstract":"<p><p>RiVax is a promising recombinant ricin toxin A subunit (RTA) vaccine antigen that has been shown to be safe and immunogenic in humans and effective at protecting rhesus macaques against lethal-dose aerosolized toxin exposure. We previously used a panel of RTA-specific monoclonal antibodies (MAbs) to demonstrate, by competition enzyme-linked immunosorbent assay (ELISA), that RiVax elicits similar serum antibody profiles in humans and macaques. However, the MAb binding sites on RiVax have yet to be defined. In this study, we employed hydrogen exchange-mass spectrometry (HX-MS) to localize the epitopes on RiVax recognized by nine toxin-neutralizing MAbs and one nonneutralizing MAb. Based on strong protection from hydrogen exchange, the nine MAbs grouped into four spatially distinct epitope clusters (namely, clusters I to IV). Cluster I MAbs protected RiVax's α-helix B (residues 94 to 107), a protruding immunodominant secondary structure element known to be a target of potent toxin-neutralizing antibodies. Cluster II consisted of two subclusters located on the \"back side\" (relative to the active site pocket) of RiVax. One subcluster involved α-helix A (residues 14 to 24) and α-helices F-G (residues 184 to 207); the other encompassed β-strand d (residues 62 to 69) and parts of α-helices D-E (154 to 164) and the intervening loop. Cluster III involved α-helices C and G on the front side of RiVax, while cluster IV formed a sash from the front to back of RiVax, spanning strands b, c, and d (residues 35 to 59). Having a high-resolution B cell epitope map of RiVax will enable the development and optimization of competitive serum profiling assays to examine vaccine-induced antibody responses across species.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00237-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35463537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 30
Protein Structure Facilitates High-Resolution Immunological Mapping. 蛋白质结构促进高分辨率免疫制图。
Clinical and Vaccine Immunology Pub Date : 2017-12-05 Print Date: 2017-12-01 DOI: 10.1128/CVI.00275-17
Madison Zuverink, Joseph T Barbieri
{"title":"Protein Structure Facilitates High-Resolution Immunological Mapping.","authors":"Madison Zuverink,&nbsp;Joseph T Barbieri","doi":"10.1128/CVI.00275-17","DOIUrl":"https://doi.org/10.1128/CVI.00275-17","url":null,"abstract":"<p><p>Select agents (SA) pose unique challenges for licensing vaccines and therapies. In the case of toxin-mediated diseases, HHS assigns guidelines for SA use, oversees vaccine and therapy development, and approves animal models and approaches to identify mechanisms for toxin neutralization. In this commentary, we discuss next-generation vaccines and therapies against ricin toxin and botulinum toxin, which are regulated SA toxins that utilize structure-based approaches for countermeasures to guide rapid response to future biothreats.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00275-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35463540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
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